Introduction

Breast cancer patients with a high-risk tumor (for example Triple Negative Breast Cancer) who achieve a pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) have a better outcome compared to patients with residual disease at surgery. This study investigated Breast Cancer Free Survival (BCFS) and predictors for distant relapse despite pCR.

Methods

Monocentric retrospective study of 243 consecutive breast cancer patients who achieved pCR (ypT0/is ypN0/N0(i+)) after treatment with NACT in UZ Leuven between 01/2000 and 08/2017. 58% had stage III breast cancer, 40% Triple Negative Breast Cancer (TNBC) and 47% HER2 pos breast cancer. BCFS was defined as any breast cancer related event (local, contra-lateral, regional, metastatic) that first appeared. Primary endpoints were frequency of BCFS and predictors for metastatic relapse: patient demographics (age, body mass index (BMI)) and tumor characteristics (TNM stage, histological type, hormonal receptor status). Secondary endpoints were breast cancer specific survival (BCSS) and overall survival (OS). Statistical analysis was performed using the Statistical Package for the Social Sciences software (SPSS, version 25). The Kaplan Meier method was used for survival analysis.

Results

Of 1167 breast cancer patients undergoing neoadjuvant treatment, 243 patients (20,8%) achieved pCR and were included. Median follow up was 57 months (range 9-252 months). 22 (9.1%) developed tumor progression; 20 (8.2%) metastatic and 2 (0.8%) contralateral. First metastatic site was the brain in 11/20 patients (55%) and 14/22 (64%) died of breast cancer. Higher clinical tumor stage at diagnosis predicted metastatic relapse (stage I-II 2.9%; stage III 12.1%). Patients with a BMI ≤25 kg/m2 had less metastatic relapse than patients with BMI >25kg/m2 (3.8% versus 12.0%), better OS (94.6% vs 88.0%) and BCSS (97.7 vs 91.7%). Neither tumor type (TNBC 8.2%; HER2-pos 8.1%; HR-pos/HER2 neg 9.3%) nor younger age < 36yrs (3.3% versus 8.9%) was prognostic for post-pCR relapse. There is a lower OS (mean 174m versus 231m, 95% CI 158-190m, median 208m) and BCSS (mean 191m versus 253m, 95% CI 182-200m) in cN1-3 versus cN0 disease at diagnosis.

Conclusion

Despite NACT-induced pCR, a small proportion (9.1%) will develop a metastatic relapse after a median follow-up of 57 months. We found that a higher stage at diagnosis and a higher BMI were prognostic for worse BCFS while age <36 y and negative hormonal receptor status were not prognostic. cN+ at diagnosis and a BMI >25 predict worse OS and BCSS.

Citation Format: Borremans K, Berteloot P, Van Nieuwenhuysen E, Han S, Hoste G, Wildiers H, Punie K, Smeets A, Nevelsteen I, Floris G, Van Ongeval C, Keupers M, Prevos R, Van Limbergen E, Menten J, Weltens C, Janssen H, Vergote I, Neven P. Breast cancer recurrence and predictors for recurrence despite pathologic complete response following neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-04.